Pharmacological effects of a synthetic quinoline, a hybrid of tomoxiprole and naproxen, against acute pain and inflammation in mice: a behavioral and docking study

Document Type: Original Article

Authors

1 Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): In the present study, we investigated the potential anti-nociceptive activity and acute anti-inflammatory effect of a synthetic quinoline compound (2-(4-Methoxyphenyl)benzo[h]quinoline-4-carboxylic acid, QC), possessing structural elements of both naproxen and tomoxiprole drugs.
Materials and Methods: The anti-nociceptive activity of QC was evaluated using chemical- and thermal-induced nociception models and its acute anti-inflammatory effect was evaluated by xylene-induced ear edema test in mice.
Results: QC displayed a dose dependent effect in both acute anti-nociceptive tests (writhing and hot plate). This compound at dose of 6.562 mg/kg showed a high anti-nociceptive effect near equal to  diclofenac 5 mg/kg. It also showed high anti-inflammatory effects (less than 6.562 mg/kg) comparable to those of reference drugs diclofenac (5 mg/kg) and celecoxib (100 mg/kg). Docking study showed that this quinoline derivative could inhibit COX-2 enzyme strongly.
Conclusion: QC showed high anti-nociceptive and anti-inflammatory effects comparable to reference drugs and can exert its anti-nociceptive and anti-inflammatory activities through COX-2 inhibition.

Keywords


1. Mukherjee S, Pal M. Quinolines: a new hope against inflammation. Drug Discov Today 2013; 18, 389-398.

2. Zarghi A, Ghodsi R, Azizi E, Daraie B, Hedayati M, Dadrass O. Synthesis and biological evaluation of new 4-carboxyl quinoline derivatives as cyclooxygenase-2 inhibitors. Bioorg Med Chem 2009; 17: 5312-5317.

3. Ghodsi R, Zarghi A, Daraie B, Hedayati M. Design, synthesis and biological evaluation of new 2,3-diarylquinoline derivatives as selective cyclooxygenase-2 inhibitors. Bioorg Med Chem 2010; 18: 1029-1033.

4. Zarghi A, Ghodsi R. Design, synthesis, and biological evaluation of ketoprofen analogs as potent cyclooxygenase-2 inhibitors. Bioorg Med Chem 2010; 18: 5855–5860.

5. Hanke T, Merk D, Steinhilber D, Geisslinger G, Schubert-Zsilavecz M. Small molecules with anti-inflammatory properties in clinical development. Pharmacol Ther 2016; 157: 163–187.

5. Imai K, Takaoka A. Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer  2006; 6: 714-727.

6. Lin WH, Kuo HH, Ho LH, Tseng ML, Siao AC, Hung ChT, Jeng KCh, Hou ChW. Gardenia jasminoides extracts and gallic acid inhibitlipopolysaccharide‐induced inflammation by suppression of JNK2/1 signaling pathways in BV‐2 cells. Iran J Basic Med Sci 2015; 18:555‐562.

7. Moallem A, Imenshahidi M, Shahini N, Javan AR, Karimi M, Alibolandi M, Ghandadi M, Etemad L, Motamedshariaty V, Hosseini T, Hadizadeh F. Synthesis, anti-inflammatory and anti-nociceptive activities and cytotoxic effect of novel thiazolidin-4-
ones derivatives as selective cyclooxygenase (COX-2) inhibitors. Iran J Basic Med Sci; 2013; 16:1238-1244.

8. Simon LS, Milis JA. Non-steroidal anti-inflammatory drugs. N Engl J Med 1980; 302:1237–1243.

9. West RE, Williams SM, She SH, Carruthers NI, Egan RW, Motasim Billah M. Tomoxiprole selectively inhibits cyclooxygenase-2. Prostaglandins 1997; 54, 891–898.

10. Ghodsi R, Azizi E, Ferlin MG, Pezzi V,  Zarghi A. Design, synthesis and biological evaluation of 4-(imidazolylmethyl)-2-aryl-quinoline derivatives as aromatase inhibitors and anti-breast cancer agents. Lett
Drug Des Discov 2016; 13, 89-97.

11. Hosseinzadeh H, Ramezani M, Salmani G. Anti-nociceptive, anti-inflamatory and acute toxicity effects of Zataria multiflora Boiss extracts in mice and rats. J Ethnopharmacol 2000; 73: 379–385.

12. Hosseinzadeh H, Ramezani M, Fadishei M. Anti-nociceptive, anti-inflammatory and acute toxicity effects of Zhumeria majdae extracts in mice and rats. Phytomedicine 2002; 9: 135 – 141.

13. Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987; 30: 103–114.

14. Vongtau HO, Abbah J, Mosugu O, Chindo BA, Ngazal IE, Salawu AO et al. Anti-nociceptive profile of the methanolic extract of neorautaneniamitis root in rats and mice. J Ethnopharmacol 2004; 92 : 317–324.

15. Vongtau HO, Abbah J, Ngazal IE, Kunle Of, Chindo BA, Otsapa PB, et al. Anti-nociceptive and anti-infammatory activities of the methanolic extract of Parinari polyandra stem bark in rats and mice. J Ethnopharmacol 2004; 90: 115–121.

16.  Bentley GA, Newton SH, Starr J. Evidence for an action of morphine and the enkephalins on sensory nerve endings in the mouse peritoneum. Br J Pharmacol 1981; 73: 325–332.

17. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001: 413: 203–210.

18. Derardt R, Jougney S, Delevalcee F, Falhout M. Release of prostaglandins E and F in an algogenic reaction and its inhibition. Eur J Pharmacol 1980; 51: 17–24.

19. Mohamad AS, Akhtar MN, Zakaria ZA, Perimal EK, Khalid S, Mohd PA, Khalid M.H, Israf DA, Lajis NH, Sulaiman MR. Anti-nociceptive activity of a synthetic chalcone, flavokawin B on chemical and thermal models of nociception in mice. Eur J Pharmacol 2010; 647: 103–109.

20. Hosseinzadeh H, Moallem SA, Moshiri M, Sarnavazi MS, Etemad L. Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice. Arzneimittelforschung 2012; 62: 324–329.

21. Zarghi A, Arfaei S. Selective COX-2 inhibitors: a review of their structure-activity relationships. Iran J Pharm Res 2011; 10: 655-683.